The invention relates to a method for determining the prognosis of a patient with a neurological disease.
Neurological diseases include Alzheimer's disease (AD), Creutzfeldt-Jakob disease, Huntington's disease, Lewy body disease, Pick's disease, Parkinson's disease (PD), amyotrophic lateral sclerosis, multiple sclerosis (MS), neurofibromatosis, and diseases without a necessary genetic component such as brain injury, stroke and multi-infarct dementia (MID). Most of these diseases are typified by onset during the middle adult years and lead to rapid degeneration of specific subsets of neurons within the neural system, ultimately resulting in premature death. There are no known cures and few therapies that slow the progression of these diseases.
Parkinson's disease (PD) is a common neurodegenerative disorder which first appears in mid- to late-life. Familial and sporadic cases occur, although familial cases account for only 1-2 percent of the observed cases. The neurological changes which cause this disease are somewhat variable and not fully understood. The disorder generally develops asymmetrically with tremors in one hand or leg and progresses into symmetrical loss of voluntary movement. Eventually, the patient becomes incapacitated by rigidity and tremors. In the advanced stages the disease is frequently accompanied by dementia.
Diagnosis of both familial and sporadic cases of Parkinson's disease can only be made after the onset of the disease symptoms. Anticholinergic compounds, propranolol, primidone and levadopa are frequently administered to modify neural transmissions and thereby suppress the symptoms of the disease, though there is no known therapy which halts or slows the underlying progression.
Multiple Sclerosis (MS) is a neurodegenerative disease of the brain and spinal cord in which a breakdown occurs in the myelin sheathing of the nerve fibers. MS is currently incurable and treatments are few and usually result in only temporary improvements of the disease symptoms.
Stroke is the sudden death of a portion of the brain cells due to a lack of oxygen. A stroke occurs when blood flow to the brain is impaired resulting in abnormal brain function. Brain blood flow can be impaired by blockage or rupture of an artery to the brain.
In the United States, about 400,000 people a year will suffer from a stroke, and up to 40% of these strokes may be fatal. The cost of strokes is not just measured in the billions of dollars lost in work, hospitalization, and the care of survivors in nursing homes. The major cost of a stroke is the loss of independence that occurs in 30% of the survivors. What was a self-sustaining and enjoyable life style may lose most of it's quality after a stroke and family members can often find themselves in a new role as caregivers.
Other cerebral vascular diseases that present similar sequelae to stroke are multi-infarct dementia (MID), vascular dementia (VaD), and cerebrovascular injury or accident. In addition, diseases such as AIDS can often have vascular dementia as a complication. As with the above diseases, there are no known cures for these diseases and most therapies only aid rehabilitation or lower the risk of having another vascular incident.
Apolipoprotein E (apoE) functions as a ligand in the process of receptor mediated internalization of lipid-rich lipoproteins. ApoE is probably also involved in reverse lipid transport. In the central nervous system (CNS), apoE plays a central role in the mobilization and redistribution of cholesterol and phospholipid during membrane remodeling associated with synaptic plasticity. The importance of apoE in the brain is further underscored by the absence of other key plasma apolipoproteins such as apoA1 and apoB in the brain.
The apoE gene on chromosome 19 has three common alleles (E2, E3, E4), which encode three major apoE isoforms. The frequency of the apoE4 allele has been shown to be markedly increased in sporadic Alzheimer's Disease (AD) and late onset familial Alzheimer's disease (AD). This gene dosage effect was observed in both sporadic and familial cases (i.e., as age of onset increases, E4 allele copy number decreases). Women, who are generally at a greater risk of developing Alzheimer's disease, show increased apoE4 allele frequency when compared to age matched men.
The cholinergic hypothesis of geriatric memory dysfunction has raised some fundamental questions regarding the heterogeneity of responses toward different cholinomimetics in AD. The absence of clear beneficial effects of choline and lecithin on geriatric patients with and without AD is still perplexing. Furthermore, multiple clinical studies using esterases inhibitors such as physostigmine and tacrine have shown that, contrary to results found in young subjects, the optimal acute dose necessary to facilitate performance on memory tasks varied considerably among individual aged subjects.
Neurological diseases provide a unique series of complications for the clinicians, patients, and care givers; the diseases often progress rapidly and disrupt a vast number of major life functions. The progressive nature of these diseases makes the passage of time a crucial issue in the choice and administration of different treatment options. It would be desirable to know the severity of the prognosis for patients diagnosed with various neurological diseases.